The substantial morbidity and mortality caused by influenza has stimulated the development of antiviral agents such as zanamivir and oseltamivir to treat and prevent acute influenza infections without the adverse effects of earlier drugs. Cooper and colleagues analyzed the evidence to determine the efficacy and safety of these two agents.
They searched electronic and other databases, references, and manufacturers' data to identify all published and unpublished randomized double-blind clinical trials of the treatment or prevention of naturally occurring influenza with zanamivir or oseltamivir. They considered three groups of patients: children (12 years and younger), healthy persons 12 to 65 years of age, and high-risk persons (65 years and older or having chronic medical conditions). The principal outcome measures were time to relief of symptoms and complications requiring antibiotic therapy. Hospital admissions and time to resumption of normal activities also were considered. For preventive studies, the principal end point was the number of persons with laboratory-confirmed symptomatic influenza.
Of 62 treatment studies identified, only eight studies of zanamivir and nine studies of oseltamivir met eligibility and quality criteria. For zanamivir, the reduction in median time to alleviation of symptoms compared with placebo ranged from 0.8 days in healthy adults to one day in children. The effect was greater (one day in children and two days in high-risk patients) in persons with confirmed influenza. The odds of complications requiring antibiotics also were reduced in two studies. Patients treated with oseltamivir showed a reduction in median time to alleviation of symptoms (0.4 days in high-risk adults and 0.9 days in children) with an increased effect in laboratory-confirmed influenza (0.4 days in high-risk adults and 1.5 days in children). Complications requiring antibiotics were reported to be less common in one study of children and one study of adults, but this difference only reached statistical significance in the influenza-positive patients.
Of the 18 trials of prevention of influenza, only three trials of zanamivir and four trials of oseltamivir met the criteria for inclusion in the analysis. Zanamivir showed an 81 percent relative reduction in the odds of household contacts developing laboratory-confirmed influenza, and oseltamivir was associated with a 90 percent reduction. Oseltamivir also was associated with a 92 percent reduction in the odds of laboratory-confirmed symptomatic influenza when used for seasonal prophylaxis in a residential elderly care facility and a 74 percent reduction in a healthy population.
The authors conclude that treatment of otherwise healthy adults or children with zanamivir or oseltamivir within 48 hours of symptom onset reduces the duration of symptoms of influenza by 0.4 days to one day and diminishes the chances of receiving antibiotics for complications by up to 43 percent. The ability of these agents to prevent influenza in exposed persons is reported to range from 70 to 90 percent, depending on the population and strategy used. Further research is necessary, particularly into the role of these drugs in preventing influenza outbreaks in children and institutionalized elderly patients.